Aims

The modulatory effects of piperine on drug metabolizing enzymes play an important role in the control of pharmacokinetic and the bioavailability properties of the administered drugs. The present study investigated the effect of piperine and piperine-donepezil co-administration on cognitive functions and synaptic plasticity at hippocampal perforant pathway (PP) to dentate gyrus (DG) synapses in an experimental model of Alzheimer's disease (AD).

Materials and methods

Intracerebroventricularly (ICV) streptozotocin (STZ) injected rats were treated once daily with piperine, donepezil and piperine combined with donepezil for 4 weeks. Cognitive performance was evaluated using passive avoidance and Morris water maze performance tasks. Analysis of evoked field potentials was done to explore possible effects on input/output response, paired-pulse facilitation and long-term synaptic plasticity (LTP) at PP to DG synapses of hippocampus.

Key findings

Rats subjected to ICV injection of STZ exhibited cognitive deficit associated with a hippocampal oxidative stress, effects that were reversed by chronic treatment with piperine or donepezil and or piperine combined with donepezil. Chronic treatment with piperine or donepezil restored the disruptive effects of STZ on LTP without altering basal synaptic transmission.

Significance

We found that optimal hippocampal function is dependent on tissue redox homeostasis. Piperine might reduce the synaptotoxic effects of STZ on hippocampal synaptic neurotransmission and correspondently is a good potential for neuroprotection against oxidative damage from ICV injection of STZ. These results suggest that piperine or donepezil significantly ameliorate cognitive deficit and LTP induction by attenuating oxidative status.

中文翻译：

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胡椒碱和胡椒碱加多奈哌齐对阿尔茨海默病大鼠模型海马突触可塑性损伤的功能作用

目的

胡椒碱对药物代谢酶的调节作用在控制所给药药物的药代动力学和生物利用度特性中起重要作用。本研究在阿尔茨海默病（AD）实验模型中研究了胡椒碱和胡椒碱-多奈哌齐共同给药对海马穿孔通路（PP）齿状回（DG）突触的认知功能和突触可塑性的影响。

材料和方法

脑室内（ICV）链脲佐菌素（STZ）注射的大鼠每天用胡椒碱，多奈哌齐和胡椒碱联合多奈哌齐治疗4周。使用被动回避和莫里斯水迷宫表演任务评估认知表演。对诱发的场电位进行了分析，以探讨对输入/输出响应，成对脉冲促进和PP至DG海马DG突触的长期突触可塑性（LTP）的可能影响。

主要发现

接受STV的ICV注射的大鼠表现出与海马氧化应激相关的认知缺陷，这种作用在胡椒碱或多奈哌齐和/或胡椒碱联合多奈哌齐的慢性治疗中得到了逆转。胡椒碱或多奈哌齐的慢性治疗恢复了STZ对LTP的破坏作用，而没有改变基础突触传递。

意义

我们发现最佳的海马功能取决于组织氧化还原稳态。胡椒碱可能会降低STZ对海马突触神经传递的突触毒性作用，相应地，它具有很好的潜在神经保护作用，可防止ICV注射STZ引起的氧化损伤。这些结果表明，胡椒碱或多奈哌齐可通过减弱氧化状态显着改善认知缺陷和LTP诱导。